53 research outputs found

    Adipose Tissue-Derived Mesenchymal Stem Cells Increase Skin Allograft Survival and Inhibit Th-17 Immune Response

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    Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4+ regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4+ T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation

    COVID-19: Impact in endothelial function and therapy with Mesenchymal Stromal Cells

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    The new pandemic of SARS-CoV-2 Betacoronavirus, has spread worldwide, and infected millions of individuals causing the disease denominated of COVID-19. Further on flu symptoms, due to the high tropism of virus, has most been observed in the COVID-19 pathophysiology: acute heart failure, thromboembolism events, acute renal failure, neurological and liver damage, and multiple organ failure, with special attention to endothelial disfunction. Hence, elucidate whether virus target the endothelium is a crucial step to understand COVID-19 pathogenesis. However, the permissiveness of blood vessels during SARS-CoV-2 infection remains unclear, but regardless endothelial infection, the vascular disfunction may occurred in response to molecular inflammatory signaling triggered by immune cells that attempt to limit infection. Thus, alternative therapies using mesenchymal stromal cells (MSCs) can change this scenario and help critically ill patients. In this reflection, we attempt to discuss COVID-19 pathophysiology with impact in endothelial function and explore the applicability of MSC-based therapies as alternative treatment.

    COVID-19: Impact in endothelial function and therapy with Mesenchymal Stromal Cells

    Get PDF
    The new pandemic of SARS-CoV-2 Betacoronavirus, has spread worldwide, and infected millions of individuals causing the disease denominated of COVID-19. Further on flu symptoms, due to the high tropism of virus, has most been observed in the COVID-19 pathophysiology: acute heart failure, thromboembolism events, acute renal failure, neurological and liver damage, and multiple organ failure, with special attention to endothelial disfunction. Hence, elucidate whether virus target the endothelium is a crucial step to understand COVID-19 pathogenesis. However, the permissiveness of blood vessels during SARS-CoV-2 infection remains unclear, but regardless endothelial infection, the vascular disfunction may occurred in response to molecular inflammatory signaling triggered by immune cells that attempt to limit infection. Thus, alternative therapies using mesenchymal stromal cells (MSCs) can change this scenario and help critically ill patients. In this reflection, we attempt to discuss COVID-19 pathophysiology with impact in endothelial function and explore the applicability of MSC-based therapies as alternative treatment.

    COVID-19: Impact in endothelial function and therapy with Mesenchymal Stromal Cells

    Get PDF
    The new pandemic of SARS-CoV-2 Betacoronavirus, has spread worldwide, and infected millions of individuals causing the disease denominated of COVID-19. Further on flu symptoms, due to the high tropism of virus, has most been observed in the COVID-19 pathophysiology: acute heart failure, thromboembolism events, acute renal failure, neurological and liver damage, and multiple organ failure, with special attention to endothelial disfunction. Hence, elucidate whether virus target the endothelium is a crucial step to understand COVID-19 pathogenesis. However, the permissiveness of blood vessels during SARS-CoV-2 infection remains unclear, but regardless endothelial infection, the vascular disfunction may occurred in response to molecular inflammatory signaling triggered by immune cells that attempt to limit infection. Thus, alternative therapies using mesenchymal stromal cells (MSCs) can change this scenario and help critically ill patients. In this reflection, we attempt to discuss COVID-19 pathophysiology with impact in endothelial function and explore the applicability of MSC-based therapies as alternative treatment

    Nasal polyposis : more than a chronic inflammatory disorder : a disease of mechanical dysfunction : the São Paulo position

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    Introduction The importance of our study lies in the fact that we have demonstrated the occurrence of mechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity. Objective To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked. Data Synthesis We propose a fundamentally new approach to intervening in the pathological process of NP, addressing biomechanical properties, fluid dynamics, and the concept of surface tension. Conclusion The incorporation of biomechanical knowledge into our understanding of NP provides a new perspective to help elucidate the physiology and the pathology of nasal polyps, and new avenues for the treatment and cure of NP

    O uso de células-tronco mesenquimais como nova perspectiva de tratamento para hemofilia b.

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    Hemophilia B is an X-linked bleeding disorder that results from a deficiency in functional coagulation factor IX (hFIX). Clinically, this disease is characterized by bleeding episodes mainly in the soft tissues, joints and muscles. The treatment is given by replacement therapy the plasmaderived FIX (pdFIX) or recombinant human FIX (rhFIX). Annoying intravenous infusions, along with the high cost of pdFIX and / or rhFIX, encouraged the development of new therapeutic approaches that allow more stable and lasting results. It is postulated that the gene therapy, insertion of functional genes into cells and / or tissues of the patient, could meet the physiological need of active FIX in a patient with hemophilia B, but the patient's immunological barriers posed a major obstacle to this therapy. Thus, the unsatisfactory results obtained with gene therapy plus the possibility of therapeutic use of mesenchymal stem cells (MSCs), considered immunoprivileged cells, directed to therapeutic approaches for the combination of gene and cell therapies, in other words, or genetic manipulation of MSCs ex vivo in order to transplant them in hosts, and thus correct efficiently and effectively the phenotype of hemophilia B. Therefore, this article reviews the characteristics of hemophilia, treatments available and the prospects for the use of MSCs in the treatment of hemophilia B.A Hemofilia B é uma doença genética ligada ao cromossomo X e consiste na deficiência do fator IX (FIX) da coagulação sanguínea. Clinicamente, essa doença é caracterizada por episódios de sangramento principalmente nos músculos, articulações e tecidos moles. O tratamento se dá pela terapia de reposição do FIX derivado do plasma (pdFIX) ou FIX humano recombinante (rhFIX). As inconvenientes infusões intravenosas, juntamente com o alto custo dos pdFIX e/ou rhFIX, incentivaram o desenvolvimento de novas abordagens terapêuticas que permitissem resultados mais estáveis e duradouros. Postulava-se que a terapia gênica, inserção do genes funcional em células e/ou tecidos do paciente, pudesse suprir a necessidade fisiológica do FIX ativo em portador de hemofilia B, contudo as barreiras imunológicas do paciente representaram um grande obstáculo para esta terapia. Logo, os resultados insatisfatórios obtidos com a terapia gênica acrescido da possibilidade de uso terapêutico das células-tronco mesenquimais (CTMs), células consideradas imunoprivilegiadas, direcionou-se as abordagens terapêuticas para a combinação das terapias gênica e celular, ou seja, a manipulação genética de CTMs ex vivo com a finalidade de transplantá-las em hospedeiros, e dessa forma corrigir de forma eficiente e eficaz o fenótipo da hemofilia B. Dessa forma, este artigo revisa as características da hemofilia, os tratamentos disponíveis e as perspectivas para uso de CTMs no tratamento da hemofilia B

    O USO DE CÉLULAS-TRONCO MESENQUIMAIS COMO NOVA PERSPECTIVA DE TRATAMENTO PARA HEMOFILIA B doi: http://dx.doi.org/10.5892/RUVRV.91.239257

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    A Hemofilia B é uma doença genética ligada ao cromossomo X e consiste na deficiência do fator IX (FIX) da coagulação sanguínea. Clinicamente, essa doença é caracterizada por episódios de sangramento principalmente nos músculos, articulações e tecidos moles. O tratamento se dá pela terapia de reposição do FIX derivado do plasma (pdFIX) ou FIX humano recombinante (rhFIX). As inconvenientes infusões intravenosas, juntamente com o alto custo dos pdFIX e/ou rhFIX, incentivaram o desenvolvimento de novas abordagens terapêuticas que permitissem resultados mais estáveis e duradouros. Postulava-se que a terapia gênica, inserção do genes funcional em células e/ou tecidos do paciente, pudesse suprir a necessidade fisiológica do FIX ativo em portador de hemofilia B, contudo as barreiras imunológicas do paciente representaram um grande obstáculo para esta terapia. Logo, os resultados insatisfatórios obtidos com a terapia gênica acrescido da possibilidade de uso terapêutico das células-tronco mesenquimais (CTMs), células consideradas imunoprivilegiadas, direcionou-se as abordagens terapêuticas para a combinação das terapias gênica e celular, ou seja, a manipulação genética de CTMs ex vivo com a finalidade de transplantá-las em hospedeiros, e dessa forma corrigir de forma eficiente e eficaz o fenótipo da hemofilia B. Dessa forma, este artigo revisa as características da hemofilia, os tratamentos disponíveis e as perspectivas para uso de CTMs no tratamento da hemofilia B
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